title: Small-molecule-induced clustering of heparan sulfate promotes cell adhesion.
abstract: Adhesamine is an organic small molecule that promotes adhesion and growth of cultured human cells by binding selectively to heparan sulfate on the cell surface. The present study combined chemical, physicochemical, and cell biological experiments, using adhesamine and its analogues, to examine the mechanism by which this dumbbell-shaped, non-peptidic molecule induces physiologically relevant cell adhesion. The results suggest that multiple adhesamine molecules cooperatively bind to heparan sulfate and induce its assembly, promoting clustering of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study showed that adhesamine improved the viability and attachment of transplanted cells in mice. Further studies of adhesamine and other small molecules could lead to the design of assembly-inducing molecules for use in cell biology and cell therapy.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Takemoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suehara
authors.forename: Heidie L
authors.initials: HL
authors.lastname: Frisco
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Sato
authors.forename: Takuhito
authors.initials: T
authors.lastname: Sezaki
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kawazoe
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Park
authors.forename: Sayumi
authors.initials: S
authors.lastname: Yamazoe
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizuhata
authors.forename: Rintaro
authors.initials: R
authors.lastname: Inoue
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Miller
authors.forename: Steen U
authors.initials: SU
authors.lastname: Hansen
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Jayson
authors.forename: John M
authors.initials: JM
authors.lastname: Gardiner
authors.forename: Toshiji
authors.initials: T
authors.lastname: Kanaya
authors.forename: Norihiro
authors.initials: N
authors.lastname: Tokitoh
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D019281:Dimerization; D015195:Drug Design; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D053667:Syndecans / Q000737:chemistry
chemical_list: D006497:Heparan Sulfate; D010879:Piperazines; D053667:Syndecans; C549555:adhesamine